Immune responses directed against schistosome antigens are responsible for the pathogenes is of a disease that threatens as many as 300 million people. At the same time experiments utilizing as immunogen radiation-attenuated cercariae have suggested that antigens capable of inducing a protective immune response against subsequent infection do indeed exist. Moreover, resistance to cercarial challenge has been induced in both mice and rats by use of monoclonal antibodies. The development of a subunit vaccine for schistosomiasis requires the identification and characterization of schistosome antigens capable of inducing immunoprophylaxis. We propose to identify potentially immunoprophylactic antigens by extending our ongoing analysis of gender-specific and pair-dependent S. mansoni antigens. We have established that schisotosome antigens of cercariae, schistosomula, and of adult male and female worms and eggs metabolically labeled with 35S-methionine show very different immunoreactivities with sera of mice chronically infected with only female, only male, or both male and female worms. We propose to compare the one- and two-dimensionally resolved gel electrophoresis patterns of these immunoprecipitated antigens with those obtained with sera of immunoprotected mice (immunized with 50 krad-irradiated cercariae). Monoclonal antibodies recognizing potentially immunoprophylactic antigens will be generated and used (1) to determine the chemical composition (amino acid or carbohydrate) of the antigenic epitopes responsible for conferring protection, (2) to determine the anatomic localization of antigens on the surface of the parasite and within the tissues of the infected host, (3) to purify the antigens for direct assays of protective activity, and (4) to identify and quantitate schistosome antigens in the circulation of infected hosts. The amino acid sequences of purified protein antigens will be determined so that potentially immunoprophylactic reagents can be prepared by recombinant DNA technology or (in the case of immunogenic oligopeptides) by direct synthesis. These synthesized antigens will also be assayed for immunoprophylactic activity and involvement in the immunopathogenesis of disease; thus we hope to identify immunogenic epitopes that confer appreciable resistance without sensitizing the host for subsequent granuloma formation.